The overall objective of this Phase 1 STTR application is to accomplish studies aimed at advancing a promising new drug candidate for the treatment of AIDS- related Pneumocystis carinii pneumonia (PCP) to human clinical trials. This will be accomplished through a plan of work to achieve the following specific aims: (1) develop a practical, economical and convergent synthesis of NPC1161 that is compatible with kilogram scale-up, future radiolabeling (for Phase II mechanism of action and pharmocokinetic studies), and prospective commercial development; (2) prepare putative metabolites of NPC1161 by chemical and/or bioconversion/biocatalysis methods; (3) develop a sensitive and quantitative analytical method(s) to detect putative metabolites (and parent drugs) in biological fluids; (4) determine in vitro uptake and toxicity to human red blood cells by NPC1161 derivatives and putative metabolites. PROPOSED COMMERCIAL APPLICATION: Potential commercial application not available.